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Measles virus induces persistent infection by autoregulation of viral replication

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ABSTRACT

Natural infection with measles virus (MV) establishes lifelong immunity. Persistent infection with MV is likely involved in this phenomenon, as non-replicating protein antigens never induce such long-term immunity. Although MV establishes stable persistent infection in vitro and possibly in vivo, the mechanism by which this occurs is largely unknown. Here, we demonstrate that MV changes the infection mode from lytic to non-lytic and evades the innate immune response to establish persistent infection without viral genome mutation. We found that, in the persistent phase, the viral RNA level declined with the termination of interferon production and cell death. Our analysis of viral protein dynamics shows that during the establishment of persistent infection, the nucleoprotein level was sustained while the phosphoprotein and large protein levels declined. The ectopic expression of nucleoprotein suppressed viral replication, indicating that viral replication is self-regulated by nucleoprotein accumulation during persistent infection. The persistently infected cells were able to produce interferon in response to poly I:C stimulation, suggesting that MV does not interfere with host interferon responses in persistent infection. Our results may provide mechanistic insight into the persistent infection of this cytopathic RNA virus that induces lifelong immunity.

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RNA sensing in persistently MV-infected B95a cells.B95a cells and persistently MV-infected B95a cells (B95a-MV) were stimulated with a complex of Poly I:C and Lipofectamine (Lipo) or with Lipo alone. Twenty-four hours later, the mRNA levels of ifnb1 (a), irf7 (b), rig-I (c), and mda5 (d) were quantified by real-time RT-PCR. Ratios against gapdh are graphed. Error bars are SD (n = 3).
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f4: RNA sensing in persistently MV-infected B95a cells.B95a cells and persistently MV-infected B95a cells (B95a-MV) were stimulated with a complex of Poly I:C and Lipofectamine (Lipo) or with Lipo alone. Twenty-four hours later, the mRNA levels of ifnb1 (a), irf7 (b), rig-I (c), and mda5 (d) were quantified by real-time RT-PCR. Ratios against gapdh are graphed. Error bars are SD (n = 3).

Mentions: It has been reported that both IFN production and signalling pathways are impaired by MV533. To investigate if IFN production and IFN signalling pathways were impaired in cells that are persistently infected with MV, we examined the responsiveness of persistently infected B95a cells to poly I:C stimulation. Poly I:C treatment induced the gene expression of IFN-β, IRF7, RIG-I, and MDA5 in B95a cells that were persistently infected with MV as well as in uninfected control B95a cells (Fig. 4a–d). Thus, it appears that the functions of vRNA-sensing and IFN signalling pathways are not impaired in these cells.


Measles virus induces persistent infection by autoregulation of viral replication
RNA sensing in persistently MV-infected B95a cells.B95a cells and persistently MV-infected B95a cells (B95a-MV) were stimulated with a complex of Poly I:C and Lipofectamine (Lipo) or with Lipo alone. Twenty-four hours later, the mRNA levels of ifnb1 (a), irf7 (b), rig-I (c), and mda5 (d) were quantified by real-time RT-PCR. Ratios against gapdh are graphed. Error bars are SD (n = 3).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5121633&req=5

f4: RNA sensing in persistently MV-infected B95a cells.B95a cells and persistently MV-infected B95a cells (B95a-MV) were stimulated with a complex of Poly I:C and Lipofectamine (Lipo) or with Lipo alone. Twenty-four hours later, the mRNA levels of ifnb1 (a), irf7 (b), rig-I (c), and mda5 (d) were quantified by real-time RT-PCR. Ratios against gapdh are graphed. Error bars are SD (n = 3).
Mentions: It has been reported that both IFN production and signalling pathways are impaired by MV533. To investigate if IFN production and IFN signalling pathways were impaired in cells that are persistently infected with MV, we examined the responsiveness of persistently infected B95a cells to poly I:C stimulation. Poly I:C treatment induced the gene expression of IFN-β, IRF7, RIG-I, and MDA5 in B95a cells that were persistently infected with MV as well as in uninfected control B95a cells (Fig. 4a–d). Thus, it appears that the functions of vRNA-sensing and IFN signalling pathways are not impaired in these cells.

View Article: PubMed Central - PubMed

ABSTRACT

Natural infection with measles virus (MV) establishes lifelong immunity. Persistent infection with MV is likely involved in this phenomenon, as non-replicating protein antigens never induce such long-term immunity. Although MV establishes stable persistent infection in vitro and possibly in vivo, the mechanism by which this occurs is largely unknown. Here, we demonstrate that MV changes the infection mode from lytic to non-lytic and evades the innate immune response to establish persistent infection without viral genome mutation. We found that, in the persistent phase, the viral RNA level declined with the termination of interferon production and cell death. Our analysis of viral protein dynamics shows that during the establishment of persistent infection, the nucleoprotein level was sustained while the phosphoprotein and large protein levels declined. The ectopic expression of nucleoprotein suppressed viral replication, indicating that viral replication is self-regulated by nucleoprotein accumulation during persistent infection. The persistently infected cells were able to produce interferon in response to poly I:C stimulation, suggesting that MV does not interfere with host interferon responses in persistent infection. Our results may provide mechanistic insight into the persistent infection of this cytopathic RNA virus that induces lifelong immunity.

No MeSH data available.


Related in: MedlinePlus